Spatial patterning of biological cues is of special interest to investigators in areas such as nerve tissue engineering, study of chemotaxis, etc., where gradients of surface-immobilized or soluble signaling molecules have been employed. To modulate the immune and/or inflammatory systems, controlled spatial and temporal release of anti-inflammatories or chemokines are desired. In addition, interfacial tissue engineering is another area that may benefit from scaffolds with biphasic and gradient distributions of another area that may benefit from scaffolds with biphasic and gradient distributions of bioactive signals. Previous diffusion- and convection-driven approaches for the generation of linear or non-linear signal gradients are simple and inexpensive, however restricted to the generation of limited set of profiles. Use of photolithographic and soft lithographic techniques (e.g., microcontact printing and microfluidics) can provide micron-level positional accuracy; however, such techniques are expensive and largely limited to two-dimensional constructs. Commercially available gravity- and motor-driven gradient makers (Gradient maker, CBS Scientific, CA; Gradient former, Jule, Inc., CT), designed for applications in electrophoresis, have been utilized in some tissue engineering studies (Shoichet group, West group), but can only create certain gradient profiles, and have only been used to fabricate gel-based scaffolds. In addition, although some of the previous techniques have been used to create three-dimensional scaffolds with spatial gradients of bioactive agents (e.g., soluble growth factor), little attention has been paid towards the controlled temporal release aspect.
Therefore it would be advantageous to have a three-dimensional scaffold for use as an endoprosthesis that can provide controlled spatial and temporal release of a suitable bioactive agent.